Abstract

Exchange of water molecules between the frequency-shifted inner-sphere of a paramagnetic lanthanide ion and aqueous solvent can shorten the T2 of bulk water protons. The magnitude of the line-broadening T2 exchange (T2exch) is determined by the lanthanide concentration, the chemical shift of the exchanging water molecule, and the rate of water exchange between the two pools. A large T2exch contribution to the water linewidth was initially observed in experiments involving Eu3+-based paramagnetic chemical exchange saturation transfer agents in vivo at 9.4 T. Further in vitro and in vivo experiments using six different Eu3+ complexes having water exchange rates ranging from zero (no exchange) to 5 × 106 s-1 (fast exchange) were performed. The results showed that the exchange relaxivity (r2exch) is small for complexes having either very fast or very slow exchange, but reaches a well-defined maximum for complexes with intermediate water exchange rates. These experimental results were verified by Bloch simulations for two site exchange. This new class of T2exch agent could prove useful in the design of responsive MRI contrast agents for molecular imaging of biological processes.

title = "T2 exchange agents: A new class of paramagnetic MRI contrast agent that shortens water T2 by chemical exchange rather than relaxation",

abstract = "Exchange of water molecules between the frequency-shifted inner-sphere of a paramagnetic lanthanide ion and aqueous solvent can shorten the T2 of bulk water protons. The magnitude of the line-broadening T2 exchange (T2exch) is determined by the lanthanide concentration, the chemical shift of the exchanging water molecule, and the rate of water exchange between the two pools. A large T2exch contribution to the water linewidth was initially observed in experiments involving Eu3+-based paramagnetic chemical exchange saturation transfer agents in vivo at 9.4 T. Further in vitro and in vivo experiments using six different Eu3+ complexes having water exchange rates ranging from zero (no exchange) to 5 × 106 s-1 (fast exchange) were performed. The results showed that the exchange relaxivity (r2exch) is small for complexes having either very fast or very slow exchange, but reaches a well-defined maximum for complexes with intermediate water exchange rates. These experimental results were verified by Bloch simulations for two site exchange. This new class of T2exch agent could prove useful in the design of responsive MRI contrast agents for molecular imaging of biological processes.",

T2 - A new class of paramagnetic MRI contrast agent that shortens water T2 by chemical exchange rather than relaxation

AU - Soesbe, Todd C.

AU - Merritt, Matthew E.

AU - Green, Kayla N.

AU - Rojas-Quijano, Federico A.

AU - Sherry, A. Dean

PY - 2011/12/1

Y1 - 2011/12/1

N2 - Exchange of water molecules between the frequency-shifted inner-sphere of a paramagnetic lanthanide ion and aqueous solvent can shorten the T2 of bulk water protons. The magnitude of the line-broadening T2 exchange (T2exch) is determined by the lanthanide concentration, the chemical shift of the exchanging water molecule, and the rate of water exchange between the two pools. A large T2exch contribution to the water linewidth was initially observed in experiments involving Eu3+-based paramagnetic chemical exchange saturation transfer agents in vivo at 9.4 T. Further in vitro and in vivo experiments using six different Eu3+ complexes having water exchange rates ranging from zero (no exchange) to 5 × 106 s-1 (fast exchange) were performed. The results showed that the exchange relaxivity (r2exch) is small for complexes having either very fast or very slow exchange, but reaches a well-defined maximum for complexes with intermediate water exchange rates. These experimental results were verified by Bloch simulations for two site exchange. This new class of T2exch agent could prove useful in the design of responsive MRI contrast agents for molecular imaging of biological processes.

AB - Exchange of water molecules between the frequency-shifted inner-sphere of a paramagnetic lanthanide ion and aqueous solvent can shorten the T2 of bulk water protons. The magnitude of the line-broadening T2 exchange (T2exch) is determined by the lanthanide concentration, the chemical shift of the exchanging water molecule, and the rate of water exchange between the two pools. A large T2exch contribution to the water linewidth was initially observed in experiments involving Eu3+-based paramagnetic chemical exchange saturation transfer agents in vivo at 9.4 T. Further in vitro and in vivo experiments using six different Eu3+ complexes having water exchange rates ranging from zero (no exchange) to 5 × 106 s-1 (fast exchange) were performed. The results showed that the exchange relaxivity (r2exch) is small for complexes having either very fast or very slow exchange, but reaches a well-defined maximum for complexes with intermediate water exchange rates. These experimental results were verified by Bloch simulations for two site exchange. This new class of T2exch agent could prove useful in the design of responsive MRI contrast agents for molecular imaging of biological processes.